RPTPα and PTPε signaling via Fyn/Yes and RhoA is essential for zebrafish convergence and extension cell movements during gastrulation

Abstract

Convergence and extension (C&E) cell movements are essential to shape the body axis during vertebrate gastrulation. We have used the zebrafish to assess the role of the receptor protein-tyrosine phosphatases, RPTPα and PTPε, in gastrulation cell movements. Both RPTPα and PTPε knockdown and ptpra−/− embryos show defects in C&E movements. A method was developed to track gastrulation cell movements using confocal microscopy in a quantitative manner and ptpra−/− embryos displayed reduced convergence as well as extension speeds. RPTPα and PTPε knockdowns cooperated with knockdown of a well known factor in C&E cell movement, non-canonical Wnt11. RPTPα and PTPε dephosphorylate and activate Src family kinases in various cell types in vitro and in vivo. We found that Src family kinase phosphorylation was enhanced in ptpra−/− embryos, consistent with reduced Src family kinase activity. Importantly, both ptpra−/− and RPTPα and PTPε knockdown induced C&E defects were rescued by active Fyn and Yes. Moreover, active RhoA rescued the RPTPα and PTPε knockdown and ptpra−/− induced gastrulation cell movement defects as well. Our results demonstrate that RPTPα and PTPε are essential for C&E movements in a signaling pathway parallel to non-canonical Wnts and upstream of Fyn, Yes and RhoA.